A multimodal cell census and atlas of the mammalian primary motor cortex
Author:
, Adkins Ricky S.ORCID, Aldridge Andrew I.ORCID, Allen ShonaORCID, Ament Seth A.ORCID, An XuORCID, Armand EthanORCID, Ascoli Giorgio A.ORCID, Bakken Trygve E.ORCID, Bandrowski AnitaORCID, Banerjee SamikORCID, Barkas NikolaosORCID, Bartlett AnnaORCID, Bateup Helen S.ORCID, Behrens M. MargaritaORCID, Berens PhilippORCID, Berg JimORCID, Bernabucci MatteoORCID, Bernaerts YvesORCID, Bertagnolli DarrenORCID, Biancalani TommasoORCID, Boggeman Lara, Booeshaghi A. SinaORCID, Bowman IanORCID, Bravo Héctor CorradaORCID, Cadwell Cathryn RenéORCID, Callaway Edward M.ORCID, Carlin BenjaminORCID, O'Connor CarolynORCID, Carter RobertORCID, Casper TamaraORCID, Castanon Rosa G.ORCID, Castro Jesus RamonORCID, Chance Rebecca K.ORCID, Chatterjee ApaalaORCID, Chen HuamingORCID, Chun JeroldORCID, Colantuoni CarloORCID, Crabtree JonathanORCID, Creasy HeatherORCID, Crichton KirstenORCID, Crow MeganORCID, D'Orazi Florence D.ORCID, Daigle Tanya L.ORCID, Dalley RachelORCID, Dee NickORCID, Degatano KyleeORCID, Dichter BenjaminORCID, Diep DinhORCID, Ding LiyaORCID, Ding Song-LinORCID, Dominguez BerthaORCID, Dong Hong-WeiORCID, Dong WeixiuORCID, Dougherty Elizabeth L.ORCID, Dudoit SandrineORCID, Ecker Joseph R.ORCID, Eichhorn Stephen W.ORCID, Fang RongxinORCID, Felix VictorORCID, Feng GuopingORCID, Feng ZhaoORCID, Fischer StephanORCID, Fitzpatrick ConorORCID, Fong OliviaORCID, Foster Nicholas N.ORCID, Galbavy WilliamORCID, Gee James C.ORCID, Ghosh Satrajit S.ORCID, Giglio MichelleORCID, Gillespie Thomas H.ORCID, Gillis JesseORCID, Goldman MelissaORCID, Goldy JeffORCID, Gong HuiORCID, Gou LinORCID, Grauer MichaelORCID, Halchenko Yaroslav O.ORCID, Harris Julie A.ORCID, Hartmanis LeonardORCID, Hatfield Joshua T.ORCID, Hawrylycz MikeORCID, Helba BrianORCID, Herb Brian R.ORCID, Hertzano RonnaORCID, Hintiryan HouriORCID, Hirokawa Karla E.ORCID, Hockemeyer DirkORCID, Hodge Rebecca D.ORCID, Hood GregORCID, Horwitz Gregory D.ORCID, Hou XiaomengORCID, Hu LijuanORCID, Hu QiwenORCID, Huang Z. JoshORCID, Huo BingxingORCID, Ito-Cole TonyORCID, Jacobs MatthewORCID, Jia XueyanORCID, Jiang ShengdianORCID, Jiang TaoORCID, Jiang XiaolongORCID, Jin XinORCID, Jorstad Nikolas L.ORCID, Kalmbach Brian E.ORCID, Kancherla JayaramORCID, Keene C. DirkORCID, Kelly KathleenORCID, Khajouei FarzanehORCID, Kharchenko Peter V.ORCID, Kim GukhanORCID, Ko Andrew L.ORCID, Kobak DmitryORCID, Konwar KishoriORCID, Kramer Daniel J.ORCID, Krienen Fenna M.ORCID, Kroll MatthewORCID, Kuang XiuliORCID, Kuo Hsien-ChiORCID, Lake Blue B.ORCID, Larsen RachaelORCID, Lathia KananORCID, Laturnus SophieORCID, Lee Angus Y.ORCID, Lee Cheng-TaORCID, Lee Kuo-FenORCID, Lein Ed S.ORCID, Lesnar PhilORCID, Li AnanORCID, Li XiangningORCID, Li Xu, Li Yang EricORCID, Li YaoyaoORCID, Li YuanyuanORCID, Lim ByungkookORCID, Linnarsson StenORCID, Liu Christine S.ORCID, Liu HanqingORCID, Liu LijuanORCID, Lucero Jacinta D.ORCID, Luo ChongyuanORCID, Luo QingmingORCID, Macosko Evan Z.ORCID, Mahurkar AnupORCID, Martone Maryann E.ORCID, Matho Katherine S.ORCID, McCarroll Steven A.ORCID, McCracken CarrieORCID, McMillen DelissaORCID, Miranda ElanineORCID, Mitra Partha PORCID, Miyazaki Paula AssakuraORCID, Mizrachi JudithORCID, Mok StephanieORCID, Mukamel Eran A.ORCID, Mulherkar ShalakaORCID, Nadaf Naeem M.ORCID, Naeemi MaithamORCID, Narasimhan ArunORCID, Nery Joseph R.ORCID, Ng LydiaORCID, Ngai JohnORCID, Nguyen Thuc NghiORCID, Nickel LanceORCID, Nicovich Philip R.ORCID, Niu Sheng-YongORCID, Ntranos VasilisORCID, Nunn MichaelORCID, Olley DustinORCID, Orvis JoshuaORCID, Osteen Julia K.ORCID, Osten PavelORCID, Owen Scott F.ORCID, Pachter LiorORCID, Palaniswamy RameshORCID, Palmer Carter R.ORCID, Pang YanORCID, Peng HanchuanORCID, Pham ThanhORCID, Pinto-Duarte AntonioORCID, Plongthongkum NonglukORCID, Poirion OlivierORCID, Preissl SebastianORCID, Purdom ElizabethORCID, Qu LeiORCID, Rashid MohammadORCID, Reed Nora M.ORCID, Regev AvivORCID, Ren BingORCID, Ren MiaoORCID, Rimorin ChristineORCID, Risso DavideORCID, Rivkin Angeline C.ORCID, Muñoz-Castañeda RodrigoORCID, Romanow William J.ORCID, Ropelewski Alexander J.ORCID, Roux de Bézieux HectorORCID, Ruan ZongcaiORCID, Sandberg RickardORCID, Savoia StevenORCID, Scala FedericoORCID, Schor MichaelORCID, Shen EliseORCID, Siletti KimberlyORCID, Smith Jared B.ORCID, Smith KimberlyORCID, Somasundaram SarojaORCID, Song YuanyuanORCID, Sorensen Staci A.ORCID, Stafford David A.ORCID, Street KellyORCID, Sulc JosefORCID, Sunkin SusanORCID, Svensson ValentineORCID, Tan PengchengORCID, Tan Zheng HuanORCID, Tasic BosiljkaORCID, Thompson CarolORCID, Tian WeiORCID, Tickle Timothy L.ORCID, Tieu MichaelORCID, Ting Jonathan T.ORCID, Tolias Andreas SavasORCID, Torkelson AmyORCID, Tung HermanORCID, Vaishnav Eeshit DhavalORCID, Van den Berge KoenORCID, van Velthoven Cindy T.J.ORCID, Vanderburg Charles R.ORCID, Veldman Matthew B.ORCID, Vu MinhORCID, Wakeman WayneORCID, Wang PengORCID, Wang QuanxinORCID, Wang XinxinORCID, Wang YiminORCID, Wang YunORCID, Welch Joshua D.ORCID, White OwenORCID, Williams EloraORCID, Xie FangmingORCID, Xie PengORCID, Xiong FengORCID, Yang X. WilliamORCID, Yanny Anna MarieORCID, Yao ZizhenORCID, Yin LuluORCID, Yu YangORCID, Yuan JingORCID, Zeng HongkuiORCID, Zhang KunORCID, Zhang MengORCID, Zhang ZhuzhuORCID, Zhao SujunORCID, Zhao XuanORCID, Zhou JingtianORCID, Zhuang XiaoweiORCID, Zingg BrianORCID
Abstract
ABSTRACTWe report the generation of a multimodal cell census and atlas of the mammalian primary motor cortex (MOp or M1) as the initial product of the BRAIN Initiative Cell Census Network (BICCN). This was achieved by coordinated large-scale analyses of single-cell transcriptomes, chromatin accessibility, DNA methylomes, spatially resolved single-cell transcriptomes, morphological and electrophysiological properties, and cellular resolution input-output mapping, integrated through cross-modal computational analysis. Together, our results advance the collective knowledge and understanding of brain cell type organization: First, our study reveals a unified molecular genetic landscape of cortical cell types that congruently integrates their transcriptome, open chromatin and DNA methylation maps. Second, cross-species analysis achieves a unified taxonomy of transcriptomic types and their hierarchical organization that are conserved from mouse to marmoset and human. Third, cross-modal analysis provides compelling evidence for the epigenomic, transcriptomic, and gene regulatory basis of neuronal phenotypes such as their physiological and anatomical properties, demonstrating the biological validity and genomic underpinning of neuron types and subtypes. Fourth,in situsingle-cell transcriptomics provides a spatially-resolved cell type atlas of the motor cortex. Fifth, integrated transcriptomic, epigenomic and anatomical analyses reveal the correspondence between neural circuits and transcriptomic cell types. We further present an extensive genetic toolset for targeting and fate mapping glutamatergic projection neuron types toward linking their developmental trajectory to their circuit function. Together, our results establish a unified and mechanistic framework of neuronal cell type organization that integrates multi-layered molecular genetic and spatial information with multi-faceted phenotypic properties.
Publisher
Cold Spring Harbor Laboratory
Cited by
13 articles.
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